Chemical reagents can affect embryo and fetal growth and development by direct action on somatic or germinal cells. Alternatively, chemical agents can produce alterations in embryo and fetal growth and development indirectly by inducing placental toxicity. The proposed study will attempt to establish a link between chemical-induced placental toxicity and alterations in fetal growth and development. Our working hypothesis is that chemical-induced placental toxicity can be associated with changes in the placental cholinergic system and subsequently changes in placental membrane function. We have developed a human placental syncytiotrophoblastic membrane model for study of the placental cholinergic system and placental membrane function. The effect of selected environmental toxicants on the placental cholinergic system, amino acid uptake, sugar transport, and ion exchange will be studied in human and animal models. An alternate mechanism of chemical-induced placental toxicity may be chemical-induced alterations of placental release of human chorionic somato-mammotropin (hCS) and human chorionic gonadotrophin (hCG). The effect of the selected environmental toxicants on release of hCG and hCS from human placental tissue will be studied. We have proposed a working hypothesis that the placental cholinergic system regulates syncytiotrophoblastic membrane permeability and stimulates release of the trophic hormones hCS and hCG. The proposed studies will elucidate mechanisms of placentotoxicity and identify those environmental toxicants which may induce placental toxicity and subsequent alterations of fetal growth and development. A nonneuronal cholinergic system is proposed to exist in spermatozoa. We have proposed the hypothesis that the spermatozoa cholinergic system regulates its fertilizing capability. The proposed study will determine the possible mechanism of environmental toxicant-induced reversible sterility. Specifically, the effects of selected metals insecticides, and chlorinated hydrocarbons on the nonneuronal cholinergic system of spermatozoa will be studied. This study will identify classes of environmental toxicants capable of producing reversible sterility as a result of long-term low-level exposure.